The present invention relates to a series of new octahydronaphthalene derivates, which are derivatives of the known compounds designated as ML-236A, ML-236B, MB-530A and MB-530B, and to a process for preparing these compounds.
In recent years, a number of compounds having the essential skeletal structure of 3,5-dihydroxy-5-[2-(1-polyhydronaphthyl)ethyl]pentanoic acid have been discovered. The first of these, which were designated ML-236A and ML-236B, have the following formulae (i) and (ii), respectively: ##STR2## and are disClosed in U.S. Pat. No.3,983,140. These compounds can exist either in the form of a lactone (shown in the formulae above) or as a corresponding free hydroxy-carboxylic acid. They have been isolated and purified from the metabolic products of microorganisms of the genus Penicillium, especially Penicillium citrinum, a species of blue mould. They have been shown to inhibit the biosynthesis of cholesterol by enzymes or cultured cells separated from experimental animals by competing with the rate-limiting enzyme active in the biosynthesis of cholesterol, namely 3-hydroxy-3-methylglutaryl-coenzyme A reductase and, as a result, significantly reduce serum chloresterol levels of animals [Journal of Antibiotics, 29, 1346 (1976)].
Subsequently, another compound having a similar structure was discovered in the metabolic products of a mould of the genus Monascus, especially Monascus ruber, and this compound, which is disclosed inter alia, in U.K. patent specification No. 2,046,737 may be represented by the formula (iii): ##STR3## This compound is referred to as "Monacolin K" in that United Kingdom patent specification, but has subsequently been, and hereinafter is, referred to as "MB-530B".
Subsequently, a similar compound, having similar antihypercholesteraemic activity, was disclosed in United Kingdom patent specification No. 2,073,193 and was given the name "MB-530A"; this compound may be represented by the formula (iv): ##STR4##
The structure common to all of these compounds is shown below as formula (v), which also shows the numbering system employed herein to identify points of attachment and/or substitution: ##STR5##
Of the compounds of formulae (i) to (iv), those having a hydrogen atom at the 3 position are called "ML-236 compounds", whilst those having a methyl group at the 3-position are called "MB-530 compounds". The compounds in which the group at the 1-position is a hydroxy group have the suffix "A" (i.e. ML-236A and MB-530A), whilst those having a 2-methylbutyryloxy group at the 1-position have the suffix "B" (i.e. ML-236B and MB-530B).
The free hydroxy-carboxylic acids corresponding to the compounds of formulae (i) to (iv) are named ML-236A carboxylic acid, ML-236B carboxylic acid, MB-530B carboxylic acid and MB-530A carboxylic acid, respectively.
All of the above-mentioned compounds have double bonds between the 4- and 10- positions and the 5- and 6- positions. The hypothetical compounds having the same structure except that the double bonds are between the 3- and 4- positions and the 10- and 5- positions are named by adding the prefix "Iso" before the name of the parent compound. Thus, the "iso" compounds corresponding to the compounds of the formulae (i) to (iv) may be represented by the following formulae (vi) to (ix): ##STR6##
As will be explained in more detail hereinafter, the nomenclature of the compounds of the invention is based upon the names assigned to the compounds having the aforementioned formulae (i) to (iv) and (vi) to (ix).